1. Field of the Invention
The present invention relates generally to remote-controlled drug deliveries into the body of animals or humans, and more particularly, to a miniature, lightweight, air-controlled minivalve portable by small laboratory animals on their head without affecting their behavior.
2. Prior Art
Drug delivery into the brain of experimental animals is a commonly used method in the academia and the pharmaceutical industry to characterize the neurobiological effects of various chemical compounds. Microdialysis is one method to deliver drugs into the brain. This procedure utilizes a microdialysis fiber implanted into a point of interest in the brain and connected to an inlet and an outlet tube. Through the inlet tube, either a control or a drug solutions is driven into the microdialysis fiber, allowing the diffusion of the drugs into the surrounding tissue, which, in turn, induces various neurobiological effects. Through the outlet tube, the control or drug solution leaves the microdialysis fiber and the point of interest in the brain.
To alternate the flow of control and drug solutions in the implanted microdialysis probe liquid switches and valves have been used. These liquid switches are large and heavy, and are therefore placed far from the animal. Because of this, with their use it takes a long time, often an hour, for the control or drug solution to reach the animal and the implanted microdialysis probe. This lengthens the experiments unnecessarily, obscures the onset and offset of the drug effects, and makes it impossible to deliver the drugs when a specific behavioral event occurs. There are various solenoid valves available, which are smaller and lighter than the valves and liquid switches. However, the available solenoid valves are unable to continuously receive a control and a drug solution, to select between these two solutions, and to direct one of them into the microdialysis probe and one of them into a waste line. As a consequence, they cannot be used for delivering drugs via the microdialysis procedure.
Various minipumps, such as osmotic or Esox pumps, are also available for drug deliveries into the body. The disadvantage of these pumps are two-fold. First, they are able to deliver only one or a maximum of two drug solutions without repositioning or refilling them in the body. As a consequence, the behavior of the subject is disturbed, confounding the obtained data and complicating the experiment. Second, these minipumps are capable of only delivering drugs and not to simultaneously extract fluids from the brain, which is readily offered by microdialysis. As a consequence, only a fraction of the neurobiological effects of the drug-effects can be detected using minipumps of the prior art.
Because of the above limitations of commercially available valves, liquid switches, solenoid valves, and minipumps, drug deliveries into the brain of experimental animals have been time-consuming, unreliable and limited in terms of extracting information from the brain. A miniature, light-weight, remotely-controlled valve is needed, which is portable by the laboratory animal on its head without interfering with its behavior, allowing the alternation of the control and drug solutions close to the brain and driving the selected solution into a microdialysis probe. This would allow the rapid delivery of drugs through the implanted microdialysis probe and the instantaneous detection of the drug-induced neurobiological effects. As a consequence, the experiments would not be time-consuming, the onset and offset of drug effects would not be obscure, and multiple drug deliveries during the occurrence of special behavioral events would be possible without affecting the subject""s behavior. Optimally, the use of such a miniature, light-weight, remotely controlled valve should be extended to the use in experiments with all types of animals, to use in humans in clinical practice, and to use in various industrial/scientific instruments. For purposes of this disclosure, the term animals includes humans.
Therefore, it is an object of the present invention to provide a minivalve for rapidly delivering drugs into the brain of freely moving animals, including small animals and primates, via a microdialysis probe connected to the minivalve and implanted into the brain of the animals.
It is a further object of the present invention to provide a system for effectively using the minivalve to rapidly deliver many drugs into the brain and to detect the drug-induced neurobiological changes instantly.
The present invention eliminates the difficulties associated with the use of traditional valves, liquid switches and solenoid valves. The invention is a miniature, light-weight, remotely-controlled valve, referred hereinafter as xe2x80x9cminivalvexe2x80x9d, which is portable by small laboratory animals on their head without interfering with their behavior. The minivalve of the present invention allows rapid drug delivery into the brain of freely moving small animals, such as mice or rats, through a microdialysis probe, and to detect the neurobiological effects of the delivered drugs instantly.
The method for delivering drugs into the brain of small animals with the use of the minivalve of the present invention comprises; the implantation of a microdialysis probe and a microelectrode into the brain of small animals, the mounting of the minivalve on the head of the small animal, and detecting the effects of drugs delivered through the microdialysis probe.
Accordingly, a minivalve for delivering one of a control solution or a drug solution to a point of interest in a small animal is provided. The minivalve has an input for a control solution and an input for a drug solution and a common output for outputting either of the control solution or drug solution to an input of a microdialysis probe implanted at a point of interest in the small animal. The minivalve further having actuation means for actuating the minivalve between first and second positions in which the control solution or drug solution is selectively input to the microdialysis probe.
Preferably, the actuation means for actuating the minivalve between first and second positions comprises a fluid switch slidably disposed within a housing. The fluid switch is preferably actuated between the first and second positions by a differential in gas pressure between first and second gas inputs, a greater gas pressure at the first gas input actuating the fluid switch into the first position and a greater gas pressure at the second gas input actuating the fluid switch into the second position. The minivalve is preferably actuated by gas, and most preferably by air. However, the actuation can be produced with a liquid instead of gas.
Also provided is a system for delivering one of a control solution or a drug solution to a point of interest in a small animal. The system comprises: a microdialysis probe implanted at the point of interest in the small animal, the microdialysis probe allowing the diffusion of the drug solution across a membrane and into the point of interest, the microdialysis probe having an input for acceptance of one of the control or drug solutions therein and an output for outputting a dialysate therefrom; a minivalve mounted on the small animal, the minivalve having an input for the control solution and an input for the drug solution, the minivalve further having a common output for outputting either of the control solution or drug solution to the input of the microdialysis probe, the minivalve further having actuation means for actuating the minivalve between first and second positions in which the control solution or drug solution is selectively input to the microdialysis probe; and a microelectrode placed adjacent to the implanted microdialysis probe to allow the detection of the effects of the delivered drugs.
Preferably the small animal is a rat, mouse, monkey or other small animal, the minivalve is mounted on the head of the small animal, and the point of interest for implantation of the microdialysis probe is in the brain of the small animal.
Still yet provided is a method for delivering one of a control solution or a drug solution to a point of interest in a small animal. The method comprises the steps of: implanting a microdialysis probe and a microelectrode at a point of interest in the small animal; mounting a minivalve on the small animal, the minivalve having an input for a control solution and an input for a drug solution, the minivalve further having a common output for outputting either of the control solution or drug solution to the input of the microdialysis probe; delivering a drug solution and/or control solution to the minivalve; actuating the minivalve between first and second positions in which the control solution or drug solution is selectively input to the microdialysis probe; and detecting the effects of drugs delivered through the microdialysis probe with the use of the microelectrodes.
Also provided are similar systems and methods for delivering one of the drug solution or control solution to an drug ejection device such as a single or multiple cannulas placed at the point of interest in the animal.